The recent development of Tc-99m labeled hepatobiliary radiopharmaceuticals with good biological properties, i.e., a high hepatocyte extraction efficiency, short hepatobiliary transit time, and low renal clearance, has resulted in a significant new tool for investigation of the hepatobiliary system. It is now feasible to noninvasively measure hepatocyte clearance and hepatobiliary transit time in a relatively independent fashion. Our objective is to evaluate the potential of Tc-99m-diisopropyl-IDA hepatobiliary imaging in: 1) detecting minimal liver disease, 2) differentiating diffuse intrahepatic cholestasis from hepatocellular disease, and 3) differentiating biliary atresia from "non-surgical" causes of neonatal jaundice. The first question will be approached primarily by quantifying the frequency distribution of transit times through the hepatic parenchyma in normal subjects and patients who are likely to have subclinical liver dysfunction, e.g., patients recovering from viral hepatitis whose liver function tests have returned to normal. As part of the initial evaluation, we plan to determine the effect of eating on the frequency distribution of transit times through the liver in comparison to fasting. A "stress" test, i.e., eating, may be more sensitive than fasting alone. This question will also be approached in an animal model of hepatocyte disease. For the second question, we propose to quantify the relationship between hepatocyte clearance and parenchymal transit times in normal subjects and in patients with varying degrees of hepatocellular disease and to compare the results to the measurement of the same parameters in patients with intrahepatic cholestasis. In addition, the same parameters will be measured in animal models of cytotoxic and cholestatic conditions induced with hepatotoxins. For the third question, the accuracy of the combination of good clearance and infinite transit time in identifying biliary atresia will be determined in infants with neonatal jaundice. Surgery and clinical follow-up will provide the diagnoses. Our preliminary experience with a few patients in each area has been very encouraging.